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Complication of Diabetes Mellitus. Laksmi Sasiarini 2011. Acute Complication of Diabetes Mellitus. Hyperglycemic Crisis Diabetic Ketoacidosis (DKA) Hyperosmolar hyperglycemic state (HHS) Hypoglycemia . KRISIS HIPERGLIKEMIA. Epidemiology. Diabetic Ketoacidosis - PowerPoint PPT Presentation
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Complication of
Diabetes Mellitus
Laksmi Sasiarini
2011
Acute Complication of
Diabetes Mellitus
Hyperglycemic CrisisDiabetic Ketoacidosis (DKA)Hyperosmolar hyperglycemic state
(HHS)
Hypoglycemia
KRISIS HIPERGLIKEMIA
EpidemiologyDiabetic Ketoacidosis Mortality rates :
< 1% (adult subjects)> 5 % (elderly and in pts with
concomitant life- threatening illnesses)
Hyperosmolar Hyperglycemic State Mortality rate 5-20 %
The prognosis of both conditions : extremes of age in the presence of coma, hypotension, and severe comorbidities
• Infection (20% - 40%) → urinary tract and lung
• CVA• Myocardial infarction• Pancreatitis• Discontinuation of or inadequate insulin
therapy• Drugs (steroids, sympathomimetics,
thiazides)
PRECIPITATING FACTORS
PATHOGENESIS
History and Physical examination History of polyuria, polydipsia, weight loss,
dehydration, weakness, and mental status change.
Physical findings : poor skin turgor, kussmaul respiration (DKA), tachycardia, and hypotension, mental status change (full alertness to profound lethargy or coma). Focal neurologic signs and seizures HHS
Nausea, vomiting, diffuse abdominal pain are frequent in pts with DKS (>50%).
Laboratory findings
• plasma glucose, serum and urine ketones, electrolytes (with calculated anion gap), osmolality, arterial blood gases
• blood urea nitrogen/creatinine• urinalysis• complete blood count with differential• electrocardiogram• bacterial cultures of urine, blood, and throat, etc• chest X-Ray
Diagnostic criteria for DKA and HHS
DKA HHS
Mild Moderate Severe
Plasma glucose (mg/dl)Arterial pHSerum bicarbonate (mEq/l)Urine ketonesSerum ketonEffective serum osmolality (mosm/kg)Anion gapAlteration in sensoria and mental
> 250 7.25–7.30 15–18 (+)(+)Variable
> 10Alert
> 250 7.00–7.2410 to 15(+)(+)Variable
> 12Alert/drowsy
> 250 < 7.00 < 10(+)(+)Variable
>12Stupor/coma
> 600> 7.30> 18SmallSmall>320
VariableStupor/coma
Anion gap : (Na+) - (Cl + HCO3) (mEq/l).
Differential diagnosis
• lactic acidosis• ingestion of drugs (salicylate, methanol,
ethylene glycol, and paraldehyde)• chronic renal failure
Protocol for the management of adult patients with HHS
Diagnostic criteria: blood glucose >600 mg/dl arterial pH >7.3 bicarbonate >15 mEq/l mild ketonuria or ketonemia effective serum osmolality >320 mOsm/kg
H2O
Na should be corrected for hyperglycemia (for each 100 mg/dl glucose >100 mg/dl, add 1.6 mEq to sodium value for corrected serum value)
TREATMENT
IV fluid (NS) ( initial : 1 l/hour; 15–20 ml · kg-1 BW · h-1)
Insulin (Continuous IV drip/im) K+ (Potssium) Bicarbonate (pH < 7) in pts with DKA
PRECIPITATING FACTOR(S)
IV FluidsHydration Status ?
Severe hypovolemia Mild dehydration Cardioogenic shock
0.9% NaCl (1 L/h) Hemodynamic monitoring
Evaluate corrected serum Na+
Serum Na high Serum Na normal Serum Na low
When serum glucose reaches 200 mg% (DKA) or 300 mg/dl (HHS), change to 5% dextrose with 0.45% NaCl at 150-250 ml/hr
0.45% NaCl (250 – 500 ml/h) depending on hydration state
0.9% NaCl (250 – 500 ml/h) depending on hydration state
INSULIN
Insulin Regular 0.1 u/kg/bolus/iv
RI 0.1 u/kg/h/iv infusion
If serum glucose does not fall by at least 10% in first hour, give 0.14 U/kg as IV bolus, then continue previous Rx
Insulin Regular 0.14 u/kg/hr as IV continuos insulin
infusion
When serum glucose reaches 200 mg/dl, reduce RI infusion to 0.02-0.05 U/kg/hr IV, or give rapid acting insulin at 0.1 U/kg SC every 2 hrs. Keep serum glucose between 150 and 200 mg/dl until resolution of DKA
When serum glucose reaches 300 mg/dl, reduce RI infusion to 0.02-0.05 U/kg/hr IV. Keep serum glucose between 200 and 300 mg/dl until px is mentally alert
POTASSIUM
Hold insulin and give 20-30 mEq K+/h until K+ >
3.3 mEq/L
Initial serum K+ ≥ 5.0 mEq/L
Give 20 – 30 mEq K+ in each liter of iv fluid (2/3
as KCL and 1/3 as KPO4) to keep serum K+ at 4 – 5 mEq/LmEq
Initial serum K+< 3.3 mEq/L
Do not give K+ and check K+ every 2 h
Initial serum K+ 3.3 – 5.5 mEq/L
BICARBONATE
pH < 6.9
NaHCO3 (100 mmol/L) dilute in 400 ml H2O + 20 mEq KCl, infuse for 2 hours
pH ≥ 6.9
No NaHCO3
Repeat every 2 h until pH ≥ 7.0 Monitor serum K+ every 2 hrs.
MAINTENANCE
Keep the serum glucose 150 – 200 mg% until metabolic control is achieved
Check electrolyte, BUN, venous pH, creatinine and glucose every 2 – 4 hours until stable
After resolution of DKA or HHS and when patient is able to eat, initiate SC multidose insulin regimen.
To transfer from IV to SC, continue IV indulin infusion for 1-2 hr after SC insulin begun to ensure adequate plasma insulin levels.
In insulin naïve pts, start at 0.5 U/kg to 0.8 U/kg body weight per day and adjust insulin as needed.
Continue to look for precipitating factor(s).
HYPOGLYCEMIA AND
DIABETES
Definition
The ADA Workgroup on Hypoglycemia defined hypoglycemia in diabetes as “all episodes of abnormally low plasma glucose concentration that expose the individual to potential harm ”.
The cutoff glucose concentration for defining hypoglycemia is controversial.
The ADA Workgroup recommended that people with insulin secretagogue or insulin treated diabetes become concerned about the possibility of developing hypoglycemia at a self-monitored (or device estimated) plasma glucose concentration of ≤ 70 mg/dL (≤ 3.9 mmol/L).
ADA classification of hypoglycemia in diabetesSevere hypoglycemia An event requiring assistance of another person to actively administer
carbohydrate, glucagon or other resuscitation actions. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Documented severe hypoglycemia
An event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration ≤ 70 mg/dL (≤ 3.9 mmol/L).
Asymptomatic hypoglycemia
An event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration ≤ 70 mg/dL (≤ 3.9 mmol/L).
Probable symptomatic hypoglycemia
An event during which symptoms typical of hypoglycemia are not accompanied by a plasma glucose determination but that was presumably caused by a plasma glucose concentration ≤ 70 mg/dL (≤ 3.9 mmol/L).
Relative hypoglycemia
An event during which the person with diabetes reports any of the typical symptoms of hypoglycemia and interprets those as indicative of hypoglycemia with a measured plasma glucose concentration >70 mg/dL (>3.9 mmol/L) but approaching that level.
Risks of severe hypoglycaemia associated with different diabetes treatment
50
40
30
20
10
0
Pat
ient
s af
fect
ed p
er y
ear (
%)
Sulphonylurea-treated type 2
diabetes
Insulin-treated type 2
diabetes
“Standard” insulintherapy in type 1
diabetes
IntensivelyTreated in type 1diabetes (DCCT)
DiAGNOSiS ??
Sign
s &
Sym
ptom
s of
HYp
oglyc
emia
Resolution of Symptom
s once Glucose Levels Rises
Low Plasma Glucose Levels
HYPOGLYCEMIAHYPOGLYCEMIA
Whipple’s Triad
Principal metabolic effects of counter-regulation in response to acute hypoglycaemia
+
++
Glucagon Vasopressin Growthhormone
Cortisol
ACTH
Hypoglycaemia
The signs and symptoms of hypoglycemia can be divided into two categories :
• Autonomic
• Neuroglycopenic
AUTONOMIC
When the blood glucose levels drop significantly, the body releases epinephrine this triggers certain processes like releasing the glucose stored in the liver (glycogen) in an attempt to stabilize the blood glucose levels. Epinephrine also affects the nervous system and results in these characteristic signs and symptoms :
AnxietyDizzinessHungerPalpitationsSweatingTrembling
NEUROGLYCOPENIC
As the blood glucose levels continue to drop without any intervention, the glucose supply to the brain is severely impaired and may result in the symptoms listed below.
Blurred visionConfusionDifficulty concentratingDrowsinessIrritability, angerPoor coordinationSpeech difficulty
Common Symptoms of Acute Hypoglycaemia in Diabetes
Autonomic Neuroglycopenic MalaiseSweatingPounding heartTremorHunger
ConfusionDrawsinessSpeech difficultyIncoordinationAtypical behaviourVisual disturbanceCircumoral paraesthesia
NauseaHeadache
Heller SR. Textbook of Diabetes 1, 2003, p.33.1
Relationships between the duration of diabetes
0-9 10-19 20-29 30-39 > 40
100
50
0
Duration of diabetes (years)
(c)
Severe hypoglycaemia without warning
100
50
0(b)
Patie
nts
affe
cted
(%) Sweating and/or tremor
Altered symtoms of hypoglycaemia100
50
0(a)
Factors that Precipitate or Predispose to Hypoglycaemia : Excessive insulin level
Excessive dosage
Error by patient, doctor or pharmacist
Increased insulin bioavailability
Accelerated absorbtion (exercise, injection into abdomen, change to human insulin)Insulin antibodies, Renal failure, Honeymoon periode
Increased insulin sensitivity
Counter-regulatory hormon deficiencies (Addison, Hypopituitarism)Weight loss, physical exercise, postpartum, menstrual cycle variation
Inadequate carbohydrate response
Missed, small or delayed mealsAnorexia nervosa, Vomiting (gastroparesis), breast feeding, failure to cover exercise
Other factors Exercise, alcohol, drugs
Heller SR. Textbook of Diabetes 1, 2003, p.33.1
Treatment of Hypoglycaemia
Established diagnosisCapillary blood sample
Oral glucose (liquid) 120 cc
Intramuscular glucagon 0.5 – 1 mg repeat after 10 ‘
Intravenous glucose 20 – 30 ml 50% dextrose
Evaluation
Maintainance 180 – 200 mg% 10%
Dextrose Dextamethasone
Komplikasi Kronik• Makroangiopati
Pembuluh darah jantungPembuluh darah otakPeripheral vascular disease
• MikroangiopatiRetinopati diabetikNefropati diabetik
• Neuropati (perifer)
United Nations (2006) :Diabetes is a global pandemic posing a serious threat to global health, acknowledging it to be a chronic, debilitating, and costly disease associated with major complications.
The greater benefits (clinical and economical) → simultaneous control of glycemia, BP, and lipid levels
The implementation of the standards of care for diabetes has been supoptimal in most clinical settings.
A recent report (Cheung et al, 2009) indicated that only 57.1% of adults with diabetes achieved an A1C of 7%, 45.5% had a blood pressure 130/80 mmHg, 46.5% had a total cholesterol 200 mg/dl.Only 12.2% of people with diabetes achieved all three treatment goals.
The American Diabetes Association’sStandards of Medical Care in
Diabetes
Summary of glycemic recommendation for non-pregnant adults with diabetes 2010A1C < 7.0% *
Preprandial capillary plasma glucose 70-130 mg/dl
Peak postprandial capillary plasma glucose < 180 mg/dl
Key concepts in setting glycemic goals :• A1C is the primary target for glycemic control• Goals should be individualized based on : - duration of diabetes - age/life expectancy - comorbid condition - known CVD or advanced microvascular complications - hypoglycemia unawareness - individual patient considerations• More or less stringent glycemic goals may be appropriate for individual patients
Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals
*Referenced to a nondiabetic range of 4.0-6.0% using a DCCT-based assay.
Summary of glycemic recommendation for non-pregnant adults with diabetes 2011
Blood Pressure Goal for Patients with Diabetes and Hypertension
Patients with diabetes should be treated to a blood pressure < 130/80 mmHg.In pregnant patients with diabetes and chronic hypertension, blood pressure target goals are 110-129 mmHg systolic and 65-79 mmHg diastolic.
• Blood pressure should be measured at every routine diabetes visit• Measurement of BPin the office should be done by a trained individual and should follow the guidelines stablished for nondiabetic individuals.
The American Diabetes Association’sStandards of Medical Care in Diabetes
Tight BP Control vs. Tight Glucose Control
Tight Glucose Control
Tight BP Control
*P < 0.05-50 -
-40 -
-30 -
0 - Stroke End Point DM Death Complications
Redu
ctio
n in
Ris
k (%
)
-20 -
-10 -
UKPDS. BMJ. 1998:317;703-712.
Treatment strategies
Patients with a systolic blood pressure of 130–139 mmHg or a diastolic blood pressure of 80–89mmHg
life style therapy* alone (max. of 3 months) targets are not achieved,
addition of pharmacological agents. (E)
* Life style therapy consists of weight loss if overweight, DASH-style dietary diet (↓sodium intake to <1,500 mg/day, ↑ consumption of fruit and vegetables to 8-10 servings/day, low-fat dairy products to 2-3 servings/day, avoiding excessive alcohol consumption, ↑ physical activity)
The American Diabetes Association’sStandards of Medical Care in Diabetes
Patients with more severe hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg)
at diagnosis or follow-up
pharmacologic therapy in addition to lifestyle therapy. (A)
• Pharmacologic therapy for patients with diabetes and hypertension → ACE inhibitor or ARB
• If needed → a thiazide diuretic should be added to those with an estimated GFR ≥ 30 ml/min per 1.73 m2 and a loop diuretic for those with an estimated GFR < 30 ml/min per 1.73 m2. (C)
Multiple Antihypertensive Agents Are Needed to Achieve Target BP
AASK MAP <92
Target BP (mm Hg)No. of antihypertensive agents
1
UKPDS DBP <85
ABCD DBP <75
MDRD MAP <92
HOT DBP <80
Trial 2 3 4
DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure.Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.Lewis EJ et al. N Engl J Med. 2001;345:851-860.Cushman WC et al. J Clin Hypertens. 2002;4:393-404.
IDNT SBP <135/DBP <85
ALLHAT SBP <140/DBP <90
Goals for Dyslipidemia Treatment in Patients with Diabetes
PRIMARY GOAL • Lowering LDL cholesterol to a target goal of < 100 mg/dl
(< 70 mg/dl with overt CVD)
SECONDARY GOAL• Lowering triglyceride levels (< 150 mg/dl) and raising
levels of HDL cholesterol (> 40 mg/dl in men and > 50 mg/dl in women).
The American Diabetes Association’sStandards of Medical Care in Diabetes
• Life style modification and increased physical activity should be recommended to improve the lipid profile in patients with diabetes. (A)
• First line drug therapy → STATIN
The American Diabetes Association’sStandards of Medical Care in Diabetes
Treatment strategies
• If drug-treated patients do not reach the above targets on maximal tolerated statin therapy, a reduction in LDL cholesterol of 30–40% from baseline is an alternative therapeutic goal. (A)
• If targets are not reached on maximally tolerated doses of statins, combination therapy using statins and other lipid lowering agents may be considered to achieve lipid targets but has not been evaluated in outcome studies for either CVD outcomes or safety. (E)
Skrining Neuropati Diabetes
Monofilament test dan persepsi getar garpu tala
Perawatan Kaki di Rumah
Patient should check feet daily Wash feet daily Keep toenails short Protect feet Always wear shoes Look inside shoes before
putting them on Always wear socks Break in new shoes
gradually
Summary• Diabetes is a chronic illnes that requires continuing medical
care and support to prevent acute complication and to reduce the risk of long-term complication.
• The common condition coexisting with type 2 diabetes (eg. Hypertension and dyslipidemia) are clear risk factor for CVD, and diabetes itself confers independent risk.
• The greater benefits (clinical and economical) of glycemic control are obtained when simultaneous control of glycemia, BP, and lipid levels has been achieved.
• Target recommendation for adults with diabetes (ADA 2011) :A1C < 7.0%Blood pressure < 130/80 mmHgLipids LDL cholesterol < 100 mg/dl
Thank You